Digital Twins: Medicine's New Crystal Ball?
Functional modeling of the state and behavior of the body or its components has the potential to provide information for clinical and research applications. The goal is to simulate how an organ, system, or even the entire body responds to stimuli and circumstances of clinical relevance to the patient, thereby deriving useful conclusions.
These models may be descriptive, predictive, prescriptive, or even generative, capable of filling in missing or unavailable data. A central challenge is accurately replicating the physicochemical, physiological, anatomical, and, when needed, psychological attributes relevant to each specific use case.
Building clinically useful digital twins depends on integrating diverse data sources, which is a technically complex task. However, when successful, it enables a dynamic 'dialogue' with the model to evaluate its current state, forecast evolution, and simulate responses to interventions such as therapies.
It is important to emphasize that digital twin simulations are tailored to individual patients — they do not represent a generic or archetypal patient but instead aim to create a personalized model for a specific individual. One example is a project led by the Spanish National Cancer Research Centre (CNIO), which is developing digital twins of women with advanced cancer using artificial intelligence. This initiative, titled 'High-Definition Oncology in Women's Cancer,' is part of the Precision Medicine Infrastructure Associated With Science and Technology program.
These digital twins consist of multiple layers of information integrated into a single model that reflects reality for a specific application.
In the aforementioned project, a wide range of data were incorporated into the digital twin models, spanning tumor metabolism, gene and protein expression, physiological indicators such as circadian rhythms, heart rate, and physical activity, emotional well-being, and conventional clinical data from diagnostics to treatment protocols.
Adding more 'layers' of information enhances the model complexity and accuracy, enabling incremental improvements and expanded functionality.
A notable innovation in this case is the biological clock model developed by the CNIO, which estimates a patient's biologic age. This can help assess whether biologic aging accelerates or slows during disease progression, providing insight into the effect of treatment. This may guide clinicians in adjusting treatment intensity or modifying therapeutic combinations according to the patient's evolving biologic state.
The layers of information used and their integration are key aspects of each type of digital twin, ensuring that it is not only functional but also clinically relevant.
In many ways, digital twins serve as 'maps,' both literal and figurative. In the most direct sense, they can guide the planning of physical interventions such as surgical procedures.
Broader Applications
In addition to simulating the effects of therapies, digital twins can model the natural progression of diseases and support long-term care planning. They may help anticipate the onset of certain conditions, particularly hereditary diseases, when risk factors are present but symptoms have yet to appear.
These models offer valuable tools for proactive risk prevention and management. In the context of prevention, the ability to present a stronger, data-driven case — even if derived from simulations — could help persuade patients and improve adherence to preventive care guidelines.
Integration With Medical Devices
From a certain perspective, digital twins resemble a technology-driven 'crystal ball.' Once refined, these models could allow clinicians to explore alternative therapeutic scenarios and identify the most effective treatment strategies. This minimizes reliance on trial and error, enabling faster data-driven decisions in a controlled simulation environment, a kind of clinical sandbox.
A key area of synergy lies between the digital twins and medical devices. Wearable technologies, for instance, can supply real-time or periodic health data that dynamically update a patient's digital twin.
Conversely, digital twins can enhance the medical device field by enabling the optimization of device configurations or implant placements. Their integration into the body and potential physiological effects can be modeled and simulated in advance, allowing for more precise and personalized interventions.
These models also help to synthesize and manage large volumes of complex data. By serving as intelligent filters, they reduce the cognitive load on clinicians, offering clear visualizations and simulations that support more confident decision-making, especially in complex or uncertain clinical situations.
Applications and Regulatory Considerations
Digital twins hold promise across a wide range of medical applications, from early diagnosis, prognosis, and personalized therapy selection to treatment monitoring and relapse prevention. In fields such as neurology, cardiology, and oncology, these models have already shown potential.
Digital twins have already been applied in neurology, cardiology, and oncology. Focusing on Spain-based developments, two recent advances featured by Univadis Spain , a Medscape Network platform, stand out: One involves using digital twins for research on the human brain to uncover mechanisms linked to psychosis remission, and the other demonstrates the use of digital twin improvements in the diagnosis of premature ventricular contractions.
While the field is evolving rapidly, it remains in its early stages. Although technical hurdles and regulatory complexities are expected, the long-term potential is significant. Digital twins could enable faster and safer evaluations of multiple treatment paths and support virtual experimentation in a risk-free environment.
One major challenge is clinical validation. Digital twins must be tested with real-world longitudinal data and demonstrate that their predictions provide added value compared to current clinical guidelines. Equally crucial is the development of interoperable, cross-border data infrastructure that enables scalable, coordinated adoption across healthcare systems worldwide.
A final and crucial aspect to consider is data privacy, ownership, and ethical use of digital twins. Beyond the data itself, fundamental questions arise about digital twin models: Who owns a person's digital twin? Should these models be transferable, and if so, under what conditions? Informed consent is central to addressing these issues and ensuring the responsible use of digital twin technologies in clinical practice.
The use of digital twins in clinical trials is already being explored, and their potential extends further to medical training and patient education, particularly in explaining therapeutic options. As technology evolves, the range of future applications continues to expand.
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Dr. Sanjay Gupta 00:00:01 'Welcome to Chasing Life. Today I'd like to start with a quick story, a very personal one for me. It was Christmas Eve, 1993 in Ann Arbor, Michigan, snowy night. It was my first year out of medical school. I was an intern in the surgery department there at Michigan. And that night I happened to be taking care of a very sick elderly gentleman who had started to develop some fluid in his chest. I was doing a procedure known as a thoracentesis. You basically put a needle into the chest to try and drain the fluid. It's a commonly done procedure and relatively simple if you know what you're doing. And frankly by that point in my training, I was sort of a pro at thoracentesis. I knew how to do it just by the book. But for whatever reason, something went wrong that night. There was bleeding, and the patient had to be rushed off to the operating room. Again, this is Christmas Eve. 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These are questions I think about our very humanity. I'm Dr. Sanjay Gupta, CNN's chief medical correspondent, and this is Chasing Life. You start the book, I gotta say, everyone should read this book. Whether you're interested in neuroscience or neurosurgery or not, you should read the book because I think these are incredible human stories. And I have three teenagers. So when I start reading about a 15-year-old named Garrett, right out of the gates, the story starts. It grabbed me. And I'm wondering if you can just transport us to that point. You get a call about this child. Talk us through what happens. Dr. David Sandberg 00:04:02 Garrett was riding an ATV without a helmet. It flipped over. He hit his head. He was unconscious. He was transported by helicopter to our hospital. He had a CT scan that showed what is a very simple problem, and I chose his case because it's so simple. We have much more complicated decisions to make than Garrett's case. This is a straightforward bread and butter epidural hematoma, a blood clot between the skull and the dura, which is the leathery covering of the brain. The problem was, when I examined him, I didn't initially detect any neurological function. His pupils were large and unreactive, a terrible sign. When I put a piece of gauze to touch his cornea, he had no corneal reflex. When I pinched him as hard as I could, he didn't move at all. And I was afraid that he had progressed to brain death. And I pinch him hard as could multiple times, not to be mean, but to assess for neurological function, and the very last time I did ... He had slight, what we call extensor posturing, where his arms went straight ahead, a sign of a severe brain injury, but a sign that he had some life. And then the question was what to do. And I wound up taking him to surgery, we saved his life, and I just had a book event in Houston and he was there, and he's amazing. He's perfect, he has no neurological problems. And I get to be the hero, but his case has haunted me because I advised his parents. I said if he were my child, I would not take him to surgery. I think the likely outcome is he's gonna progress to brain death or be neurologically absolutely devastated, not the child you've known or loved. And what a mistake I almost made. His case haunts me and I wonder, I can't think of examples, but have I made mistakes like that that I could have saved a life and didn't? I don't know the answer to that question. Dr. Sanjay Gupta 00:05:48 That is, that's existential sort of thinking there. The idea that you then reflect on other cases and say, let me think through my decision tree. Did I make the right decision based on everything? You made the right decisions. Obviously, Garrett did really well. I think you're write about the fact that he became an athlete, was on the golf team, and obviously nuclear power, studying nuclear power. 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Dr. Sanjay Gupta 00:06:59 How explicit do you think physicians should be when they're guiding a family through this question of whether to operate or not? So you know that the family is going to ask you you're obviously the expert what should we do should we operate or no and as you point out with Garret's case the the initial instinct was not to operate because I think the concern as you're sort of describing it now and in the book is that are you prolonging his death? Are you extending his life? How do you, how do you convey that to a family? Dr. David Sandberg 00:07:32 'It's hard. I mean, in terms of the parents, you know, there are some cases that are very black and white where they would be wrong to deny surgery or be wrong to do surgery. The hard ones are the gray ones. And I think you got to just be honest. You got to say, listen, this is gray. This could go terribly. He could progress to brain death or, perhaps, he might not be the child that you've known and loved and raised. We might do this operation and save his life, and he may never talk or walk again, may never be the same child you've loved, may not understand commands when spoken to, may be fed by tubes and require 24-7 nursing care. There are some who would want that at all costs. They want their child to be alive, and that's okay. There are many who wouldn't for their loved one, and that's OK too. So you have to have the honest conversation and convey the uncertainty. And I tried to do that with Garrett's parents. I told them, I'm not sure. I'm sure what the right thing is to do here. I haven't seen anybody in Garrett's exact circumstance have as good of an outcome as he has had. For every Garrett, there are many, many children who are neurologically devastated, who you wonder, did you do the right thing operating? And so, there is no right answer. You just have to convey the truth. In most circumstances, parents don't have a lot of time to make a decision. It's their whole world. And they will ask you to do everything that is possible to save their child's life. And it's a judgment call whether to proceed with surgery or not in many circumstances. Dr. Sanjay Gupta 00:09:00 There is a inflection point between hope and honesty. And they both have value. Honesty has obvious value, objective intrinsic value. I have come to believe that hope has value in and of itself as well, just as a sort of another thing to add into the mix. Just hope, maybe hope leads to better outcomes. Hard to objectify that, but I think there's something there. As a pediatric neurosurgeon, how do you find that balance between hope and honesty? Dr. David Sandberg 00:09:32 I try not to take away hope, except when there is no hope. Dr. Sanjay Gupta 00:09:36 In Garrett's case, it did feel like there was no hope, I mean, he essentially had an exam that revealed that he was brain dead. So it was very, very difficult to find hope there I imagine. Dr. David Sandberg 00:09:52 'By the grace of God, I pinched him one last time and got some slight neurological function and his brain looked good on the CT and I thought maybe we should give him a chance. This is what his parents want and so we went ahead and did that. My biggest interest within neurosurgery has been in pediatric neuro-oncology in children with malignant brain tumors. I find hope so important in those circumstances. I've taken care of many children who've been told that their brain tumor is incurable at this point and they should pursue palliative care. And we've enrolled some children like that in some of our clinical trials. And some of those patients have gained extra months or even years of life. Most of them have failed miserably. And we did provide hope to some families. And I think that hope was important, even if the ultimate outcome is the child died because the family felt as if they left no stone unturned. And that hope, even if temporary, was incredibly meaningful to them. Dr. Sanjay Gupta 00:10:54 Yeah, it's tough. These are big topics that we're sort of delving into, but the idea of preserving life at all costs versus being the honest broker as a pediatric neurosurgeon and saying, look, life is the ultimate goal, obviously, here, but let me lay down some of the scenarios of what may happen. These are brutal conversations to have with people. You do it all the time as a pediatric neurosurge, and I do it sometimes as well as an adult neurosurgery, but these are tough conversations. Dr. David Sandberg 00:11:24 Yeah, and the hard thing is that, you know, families deserve days to weeks to make those decisions. But in an acute setting, you've got minutes, you know, because if you are going to take out that blood clot, you better do it quickly because time is brain. It matters how quickly you get that blood clot out and take the pressure off the brain. So imagine you're a parent and you have to make that decision, which has so much And you have no time to do it. You have no time to call a friend. You have no time to, you know, get advice from anybody except for the nurse who you've literally just met two seconds ago. It's an impossible situation for parents. Dr. Sanjay Gupta 00:12:06 You train residents and obviously teach medical students. Now, do you explicitly teach them about this? The idea of having these tough conversations, is that trainable? Dr. David Sandberg 00:12:17 Oh, it certainly is. You know, I received no training in any time in my medical career on how to have a difficult conversation with family. I take that responsibility very seriously. I'm in academic medicine. Every time I have a conversation with a family that is going to be a difficult conversation, I look around and I grab the nearest resident medical student, whoever's the youngest person, and I come with me and I tell them what I'm going to say as I'm walking quickly into the room. Afterwards, first I check on them to make sure they're okay, and then I tell them these conversations are really important. You should absorb the things that I did that you think are positive and maybe some of the things struck you the wrong way, but you should watch other people have these difficult conversations with families and take the best of what you see and discard the worst and develop your own style, but think very carefully about how you're going to talk to a family who's undergoing the worst tragedy and imagine yourself and their shoes. Yeah, I take that responsibility incredibly seriously. I hope that's something I've done over the course of the decades for a number of people. Dr. Sanjay Gupta 00:13:23 'I'm talking with pediatric neurosurgeon and author, Dr. David Sandberg. We'll be right back. I am curious, going back to Garrett's story, first thing you said was, you know, you get this call about a 15-year-old who was ejected from an ATV not wearing a helmet. You threw that into the first line of the description. So when you hear not wearing a helmet, what's the first thing that goes through your mind? Dr. David Sandberg 00:13:53 What a shame. As a neurosurgeon who's taken care of trauma patients for years, I haven't seen anyone who's had a devastating head injury who is wearing a helmet, but I've seen so many kids and adults who are riding bikes and are hit by cars and they hit their head on the pavement and they're never the same person or they die as a result of that injury. So some parents will tell me their teenager won't wear the helmet. I say, well, then take away the bicycle. You know, this is that important. Dr. Sanjay Gupta 00:14:22 Do you think that we do enough as a society to protect our children? I mean, you have this entire chapter of the book just basically about keeping children safe. So this is the preventative aspects of neurosurgery, right? You think about prevention and infectious diseases and primary care, but as neurosurgeons, we have to think about prevent as well. Helmets, seat belts, tackle football, keeping guns in the house. As a society, should we be doing more to keep our kids safe? Dr. David Sandberg 00:14:52 'We should be doing more and we're not doing enough, you know, gun safety is a big thing in Texas, you can argue about gun regulations and this and that, but I think one thing that everybody can agree upon is if you're going to have guns in your home, please lock them up in a safe that is away from children they have no access to. I've seen four-year-olds who have access to a gun who shoot themselves in the head and they die. I've seen, you know, a twin shoot his brother. These are kids under the age of 10. They have no idea what they're doing. They think it's a toy and that family is devastated. That kid will never be the same. How will he live with himself that he shot his twin brother? How do you recover from that? These are such preventable tragedies. Tackle football is a little more controversial. I think there are some things we can all agree on. We can talk about football if you wish, but I think some things we should all agree on bicycle helmets, gun safety, you know, things like that. Dr. Sanjay Gupta 00:15:52 Yeah, I just often struggle with with the idea that we do all these amazing things in medicine develop new therapeutics and new techniques and all that and yet sometimes we just don't get the little stuff, right? It breaks my heart when I see somebody who has a totally preventable injury and I've seen ATVs go cruising by you know and places that I've been and bunch of kids on there without helmets and it just makes my heart stop. And I don't know how to find that balance. I don't want to be the guy that goes out there and yells at him, you know, like get off my lawn, you know that kind of guy, but on the other hand, I feel like we're sort of obligated to do it and in a tough way. You have this another chapter in the book, the triumphs and struggles of a pediatric neurosurgeon. And we've talked a lot about this already, but what aspects of the job do you think you struggled with the most? What are you still bad at, if I can ask that? Dr. David Sandberg 00:16:52 I don't know what I'm bad at, but I think what I've struggled with the most is coming to terms with when a child is worse after surgery than before. You can take two children with brain tumors in the same location of the brain. You operate on one of them, they wake up perfectly. You get an MRI afterwards, the tumor's out, the parents are so grateful. Everything's wonderful. You can do the exact same operation. The next day in a child with an MRI that looks the same, the tumor's in the same location, and the child wakes up with a profound neurological deficit. And you wonder, I did the same operation in these two children. Why does one of them have this problem? And sometimes, if you're honest, you have an answer. You did something that you shouldn't have done. More often than not, you don't. And that's something that was hard to come to terms with. Dr. Sanjay Gupta 00:17:44 Yeah, that's got to be pretty profound. If you're that far in your career and you just think maybe it was me, if this patient had been cared for by somebody else, they wouldn't have had that sort of outcome. What do you do with that information then if you think that that might be the case? Dr. David Sandberg 00:17:58 I think there are some neurosurgeons who you might say, you have a terrible complication and you might you know what, I trained at the best places, I did my very best, there's nothing anybody else could have done differently and you kind of wash your hands of it, right? And you don't think further about it. I think if you take that attitude, you probably shouldn't be a neurosurgeon or a surgeon or maybe a doctor at all if you're that flippant about it. The other extreme is there are some who take so much shame and internalize it so. Harshly that they can't go on and do the next operation. They don't offer that difficult surgery to the next patient. And after going through all the years of training, I don't think that's doing anybody any favors either. I think there's a happy medium in between those two extremes. The happy medium is you have deep, honest reflection. I've lost a lot of sleep on nights that follow when a patient wakes up worse after surgery. And you're honest with yourself about every step of the process. Did I assess the case carefully? Was surgery the right thing to do? Did I choose the right surgical approach? Did I discuss the risks adequately with the family? Did I discussed the risk that actually happened? Did I make the right decisions in surgery? And then afterwards, you present that case in a morbidity and mortality conference, which is one of the most important things we do. It's very hard. Imagine yourself, you have the worst day of your life. And then that worst day of your life is presented with a room of 50 to 100 people. Your boss is in the room, there are students in the room, they're strangers, there people you don't know, and they outline the worst day in your life with pictures and video, and you have to sit there and listen and absorb it. It's actually hard to do, but it's such an important thing. And I learned so much. And ultimately, what I learned is, you know, I'm not going to not do a case because I'm worried it's going to end up in morbidity and mortality conference. I'm going to do the right thing for every child. And if there's a small amount of hope, if I can help someone, even if someone like Garrett would be a good example of that, there was a high probability of Garrett's case ending up in morbidity and mortality conference because there was high probability that him progressing to brain death or devastating outcome. And then somebody in that conference is going to say, Dr. Sandberg, why did you do that operation on that kid with blown pupils who had no neurologic status? But I was You know, morbidity and mortality conference was the farthest thing from my mind when making that difficult decision, but it's out there. Dr. Sanjay Gupta 00:20:22 'M&M, morbidity and mortality. Some institutions call it DNC, Death and Complications Conference. It is one of the more unique traditions, I think, in medicine where, as you say, people get up and talk about the worst sort of outcomes in their patients, and it's incredibly humbling. It's all done in the spirit of learning, I think for the individual to learn, but also everyone else in the room to learn from this. So these types of things don't happen again. I gotta tell you, going back to the story I told you at the beginning about this thoracentesis procedure I did, where again, putting a needle into the chest to drain fluid and the patient had bleeding. I had to present that, I was an intern, and it was presenting it to all the senior residents, chief residents, attendings, everyone else that was in the room. And I remember it was, I, was, you know, incredibly nervous up there, I'd never done that before. And I finished outlining the entire presentation of what exactly happened. And the room was just silent for, it felt like 10 minutes, but it was probably like 30 seconds or 15 seconds. And then Dr. Laser Greenfield, who was our chairman of surgery at the point, was sitting there sort of moderating. And he says to me, he goes, what size needle did you use for the thoracentesis? And I told him, I said, yes, I used this size needle. It's the same needle that comes in the kit, thoracentesis kit, the standard needle. A long pause and he says, the reason I ask is because when this exact same thing happened to me back when I was a resident, blah, blah blah blah. And I remember the air just came out of the room. Everyone just exhaled because it had happened to Dr. Lazer Greenfield, this exact thing. He had thrown me a lifeline in many ways, I think, just to sort of help me get over that because I wanted to quit. I was an intern and I thought maybe, maybe this isn't right for me. Maybe this field isn't right for me, I hurt somebody. And I'm not sure that I can bounce from that. But then, you know, you get a well-intentioned, well-meaning professor, I'm sure you've done this for your residents as well, who in their own way, throws you a lifeline and says, hey, it happens, you're a good doctor, you're gonna get beyond this and you're going to do a lot of good in the world. It's really important. Dr. David Sandberg 00:22:37 Oh yeah, I remember one of the most impactful experiences of my early residency, there was a patient who had had a spine surgery and the patient had a drain that needed to be pulled, a very simple procedure that's done by residents at the bedside, and I tried to pull out the drain and it snapped off and broke and that required a second operation and it was a very big deal because it was the patient who, you know, was very upset, had been through a lot. And it was gonna be hard to talk to her about it and she's gonna need another surgery. And I was young and it a mistake that I made. And the attending neurosurgeon, his name is Mark Bilsky, he was so kind to me, but he treated me with such kindness that I think it led to me being kinder to residents who made mistakes when I was the attending, when I the boss. And I'm so grateful to Dr. Bilsky for that. All right, let's see we get the Dr. Sanjay Gupta 00:23:34 We get to give shout outs to our mentors here today as well. So Dr. Greenfield, if you're listening, Dr. Bilsky, if you're listening, you made an impact on us, you know, so we appreciate it. I just, we're getting close to the end here, but I just wanted this, this idea of finding that inflection point again, between hope and honesty. You talk a lot about this in the book, the power of hope. It drives parents to do these incredible things, search the world, travel the world in search of clinical trials, oftentimes at great personal expense. Children battling cancer inspires people to keep researching. Is hope always a good thing in medicine? Dr. David Sandberg 00:24:13 'It's hard to say, you know, I think, I'll give you one example where it's the most difficult, the most challenging. The worst disease I treat is called diffuse midline glioma. This is the equivalent or worse of pancreatic cancer in a child. It happens to children typically in the second half of the first decade of life. They have tumors that are intrinsic to the brainstem that cause the brain stem to swell. They're not amenable to surgical resection. You can't do surgery on them. Radiation therapy helps temporarily for a few months, but never cures anybody. And no chemotherapy drug alone or in combination has ever worked. And there are clinical trials that are available, but the overwhelming results of those clinical trials are disappointing. It's essentially a death sentence. And so is hope useful in that circumstance? I don't know. You know, I tell parents always that I am not God, and there are no 100 percents in life or in medicine. But in this circumstance, I know what's gonna happen. And I haven't seen a child be a long-term survivor of this particular condition. It doesn't eliminate anyone's hope. It doesn' eliminate their prayers. I don't know if it's well-served, but who am I to deny hope to a family, even in the very, very worst circumstance? Dr. Sanjay Gupta 00:25:37 Yeah, as we talked about earlier, I think hope has intrinsic value. I do worry sometimes, David, that people prey on vulnerable families in those situations, offering up, quote unquote, miracle cures and things like that, oftentimes for their own profit motivations and things like that. And I think we do, as physicians, have to insulate from that. But it's challenging, because if you think, hey, I'm willing to do anything. Save my child. I'm willing to do anything even if it's got no data behind it or even negative data behind. I am willing to give it a shot. It's tough and I think sometimes as physicians obviously we're caring for them, we're operating on them, but I think we often have to be guiding them and their families as well as they navigate that. And I think one of the things that I do, I will just really empathetically try and put myself in their shoes. Just truly put myself in their shoes. And it's hard to do. That is my kid on the table. That is my kid who's in the office and say, what would I do? It's tough to sort of navigate that. Give us one last plug on the book. Why did you title it the way that you did? Dr. David Sandberg 00:26:52 So I titled, you know, it's called Brain and Heart, the Triumphs and Struggles of a Pediatric Neurosurgeon. I go through the triumphs, which are the amazing highs to save a child's life. You know, It's like saving the entire world and to do an operation and go out and tell a family that their loved one is gonna be okay, is a high that I've been so blessed to experience and struggles because I let you into my mind. To know that some of what we do is really hard to cope with. There are situations that make us question ourselves, even the most confident among us. And there are situations in which we're affected. We shed tears, we are humans. That's the title of the book. Dr. Sanjay Gupta 00:27:39 It's a great book. David, I congratulate you. I hope everyone gets a chance to read it. Whether you're interested in medicine or not, whether you're into neurosurgery or not. These are human stories and congratulations. And thank you for sharing it with us. Dr. David Sandberg 00:27:53 Coming from you. It's an incredible honor to hear those words. Thank you so much, Dr. Gupta.
